Type 1 diabetes (T1D) is an autoimmune disease in which an inappropriate self-directed immune response affects and destroys
insulin-producing β-cells in pancreatic islets leading to dysregulated blood glucose levels. T1D may affect people of any
age, its clinical presentation is highly variable, and its incidence is increasing worldwide (1). The initial triggering events of T1D are unknown and their elucidation is of pivotal importance. Several factors might
lead to the breakdown of β-cell–specific T-cell tolerance, including genetics, exogenous infectious pathogen, noninfectious
environment agents, endogenous superantigens, or physiological stress events (2).

The hallmark of autoimmune diabetes is insulitis, which progresses to a destruction of β-cells that results in clinical T1D.
An altered balance between proinflammatory T-helper type 1 (Th1)/Th17 cells (γ-interferon [IFN-γ], interleukin [IL]-17) and
Th2 immune response (IL-4, IL-10) leads to T1D (3,4). Evidence also suggests that both genetic and environmental factors may induce local inflammatory response, where activated
intraislet dendritic cells (DCs) prevent peripheral T-cell tolerance (5). Moreover, it has been recently demonstrated that the development of destructive insulitis is partly due to impaired islet-resident
Foxp3+ regulatory T cells (6,7).

Several animal experimental models have been used for the investigation of the pathogenesis of T1D and it appears that a NOD
mouse is the model of choice. NOD mice spontaneously develop early peri-insulitis and later intraislet insulitis caused by
autoreactive T cells, …